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28

Mar

2013

Why Prioritize SENS Research for Human Longevity?

Why do I vocally support rejuvenation research based on the Strategies for Engineered Negligible Senescence (SENS) over other forms of longevity science? Why do I hold the view that SENS and SENS-like research should be prioritized and massively funded? The short answer to this question is that SENS-derived medical biotechnology has a much greater expected utility - it will most likely produce far better outcomes, and at a lower cost - than other presently ongoing lines of research into creating greater human longevity.

What is SENS?

But firstly, what is SENS? It is more an umbrella collection of categories than a specific program, though it is the case that narrowly focused SENS research initiatives run under the auspices of the SENS Research Foundation. On the science side of the house, SENS is a synthesis of existing knowledge from the broad mainstream position regarding aging and the diseases of aging: that aging is caused by a stochastic accumulation of damage at the level of cells and protein machinery in and around these cells. SENS is a proposal, based on recent decades of research, as to which of the identified forms of damage and change in old tissues are fundamental - i.e. which are direct byproducts of metabolic operation rather than cascading effects of other fundamental damage. On the development side of the house, SENS pulls together work from many subfields of medical research to show that there are clear and well-defined ways to produce therapies that can repair, reverse, or make irrelevant these fundamental forms of biological damage associated with aging.

Present arguments within the mainstream of aging research are largely over the relative importance of damage type A versus damage type B, and how exactly the extremely complex interaction of damage with metabolism progresses - but not what that damage actually is. A large fraction of modern funding for aging research goes towards building a greater understanding this progression; certainly more than goes towards actually doing anything about it. Here is the thing, however: while understanding the dynamics of damage in aging is very much a work in progress, the damage itself is well known. The research community can accurately enumerate the differences between old tissue and young tissue, or an old cell and a young cell - and it has been a good number of years since anything new was added to that list.

If you can repair the cellular damage that causes aging, it doesn't matter how it happens or how it affects the organism when it's there. This is the important realization for SENS - that much of the ongoing work of the aging research community is largely irrelevant if the goal is to get to human rejuvenation as rapidly as possible. Enough is already known of the likely causes of aging to have a reasonable expectation of being able to produce laboratory demonstrations of rejuvenation in animal models within a decade or two, given large-scale funding.

Comparing Expected Values

Expected value drives human endeavor. What path ahead do we expect to produce the greatest gain? In longevity science the investment is concretely measured in money and time, and we might think of the expected value in terms of years of healthy life added by the resulting therapies. The cost of these therapies really isn't much of a factor - all major medical procedures and other therapies tend to converge to similar costs over time, based on their category: consider a surgery versus an infusion versus a course of pills, for example, where it's fairly obvious that the pricing derives from how much skilled labor is involved and how much care the patient requires as a direct result of the process.

On the input side, there are estimates for the cost in time and money to implement SENS therapies for laboratory mice. For the sake of keeping things simple, I'll note that these oscillate around the figures of a billion dollars and ten years for the crash program of fully-funded research. A billion dollars is about the yearly budget of the NIA these days, give or take, which might be a third of all research funding directed towards aging - by some estimates, anyway, though this is a very hard figure to verify in any way. It's by no means certain the that the general one third/two thirds split between government and private research funding extends to aging research.

On the output side, early SENS implementations would be expected to take an old mouse and double its remaining life expectancy - e.g. produce actual rejuvenation, actual repair and reversal of the low-level damage that causes aging, with repeated applications at intervals producing diminishing but still measurable further gains. This is the thing about a rejuvenation therapy that works; you can keep on applying it to sweep up newly accruing damage.

In the case of sirtuins, money has certainly flowed. Sirtris itself sold for ~$700 million, and it's probably not unreasonable to suggest that a billion dollars has gone into broader sirtuin-related research and development over the past decade. What does the research community have to show for that? Basically nothing other than an increased understanding of some aspects of metabolism relating to calorie restriction and other adaptations that alter life span in response to environmental circumstances. Certainly no mice living longer in widely replicated studies as is the case for mTOR and rapamycin - the sirtuin results and underlying science are still much debated, much in dispute.

The historical ratio of dollars to results for any sort of way to manipulate our metabolism to slow aging is exceedingly poor. The thing is, this ratio shouldn't be expected to get all that much better. Even if marvelously successful, the best possible realistic end result of a drug that slows aging based on what is known today - say something that extracts the best side of mTOR manipulation with none of the side-effects of rapamycin - is a very modest gain in human longevity. It can't greatly repair or reverse existing damage, it can't much help those who are already old become less damaged, it will likely not even be as effective as actual, old-fashioned calorie restriction. The current consensus is that calorie restriction itself is not going to add more than a few years to a human life - though it certainly has impressive health benefits.

(A sidebar: we can hope that one thing that ultimately emerges from all this research is an explanation as to how humans can enjoy such large health benefits from calorie restriction, commensurate with those seen in animals such as mice, without also gaining longer lives to match. But if just eating fewer calories while obtaining good nutrition could make humans reliably live 40% longer, I think that would have been noted at some point in the last few thousand years, or at least certainly in the last few hundred).

From this perspective, traditional drug research turned into longevity science looks like a long, slow slog to nowhere. It keeps people working, but to what end? Not producing significant results in extending human longevity, that's for sure.

Ergo...

The cost of demonstrating that SENS is the right path or the wrong path - i.e. that aging is simply an accumulation of damage, and the many disparate research results making up the SENS vision are largely correct about which forms of change in aged tissue are the fundamental forms of damage that cause aging - is tiny compared to the cost of trying to safely eke out modest reductions in the pace of aging by manipulating metabolism via sirtuins or mTOR.

The end result of implementing SENS is true rejuvenation if aging is caused by damage: actual repair, actual reversal of aging. The end result of spending the same money and time on trying to manipulate metabolism to slow aging can already be observed in sirtuin research, and can reasonably be expected to be much the same the next time around the block with mTOR - it produces new knowledge and little else of concrete use, and even when it does eventually produce a drug candidate, it will likely be the case that you could do better yourself by simply practicing calorie restriction.

The expectation value of SENS is much greater than that of trying to slow aging via the traditional drug discovery and development industry. Ergo the research and development community should be implementing SENS. It conforms to the consensus position on what causes aging, it costs far less than all other proposed interventions into the aging process, and the potential payoff is much greater.

Comments

Hello, I was wondering if there has been much outreach to wealthy industrialists or philanthropists regarding funding the SENS approach. I would think someone like Bill Gates, or Elon Musk, someone that understands the potential gains and has the capital and vision to execute on this, could make an enormous difference.

Posted by: Greg at March 28th, 2013 5:29 PM

Hello Greg,

Yea, I are really surprised that the wealthy (especially the younger ones such as the Google boys)individuals could not easily understand how this organization would benefit them in a reasonable short time. They have alot more to lose (money and power) in growing old and dying than us less wealthy people.

I belive Peter Thiel is involved, but very few others of this caliber. It would be great to have some kind of outreach program to solicitate this group for assistance in the funding department and to help make this organization become more mainstream.

I have made similar comments in this web site about the exact thing.

Posted by: Robert Church at March 28th, 2013 7:25 PM

@Reason,

I'll tag on to what Greg and Robert are saying - can you perhaps post something on Nursultan Nazarbayev, the president of Kazakhstan, and how he wants aging defeated and is extremely wealthy? I think there is a possibility there.

I think this also benefit all readers here at Fight Aging!

Thanks!
VV5

Posted by: VV5 at March 28th, 2013 10:52 PM

I think that the writer is massively undervaluing the potential value of both CR mimics and pure research.

A good CR mimic could add years to the average human lifespan, and unlike SENS-style research, it could happen soon; a number of substances have already been shown to slow aging in mice and in other mammals. If we come to understand how this mechanic works, it's going to be a huge boon in anti-aging research, and it could produce practical results in the very near future, adding years of human lifespan. Once any kind of anti-aging drug goes into general use, once there is some kind of proof of concept that aging in humans isn't something fixed, that it's something that can be changed, the field is going to explode, and the amount of money that is going to flow into things like SENS is going to increase tenfold.

Also, it's a basic axiom that unsentimental research always pays off in the end. The better we understand aging, the more likely we are to be able to treat it, and we're likely to discover other things that will have other uses, including some we haven't even thought of yet. Fundamental research always deserves funding.

Basically, the main goal here shouldn't be trying to get people to fund one specific type of research over others, the goal should be to increase the visibility of the whole field, and to get both the government and investors more interested in investing money into really anything in biology or medicine and into anti-aging medicine specifically.

Posted by: Yosarian at March 29th, 2013 11:04 AM

I have been a huge fan of SENS ever since I first watched Aubrey de Grey's Ted Talk on aging. I am commenting because I have a question. What can ordinary people like me do to support SENS? In other words, how can I help?

Posted by: Alain at April 6th, 2013 7:34 PM

@Alain: Donate to the SENS Reseach Foundation, and persuade others to do the same. Funding is the limiting factor for progress in SENS:

Maybe some of us can try to reach out to the multi-billionaires and try to get them to see the benefit of funding longevity-focused research? People like Bill Gates, Oprah, to name a few. do they have foundations and websites on which we can make suggestions?

Overcoming the barrier of prejudice and ignorance is not easy. The history show this all the time. We must hope that all goes well and decanted, probably within 70 years, and we can see results on this matter of extending human life. People who have a lot of money in the world, do not have to be very smart, with rare exceptions, so we must should not expect much from them. Something similar can be said of artists, athletes and generally all those who make fortunes for the love of the public.

Forbes also lists 1600 billionaires worldwide, 386 of which are Americans.

Futurist Ray Kurzweil works at powerful Google. Why can he (and Eric Drexler and others) get in touch with some of those billionaires above and with Microsoft, Apple, and other high-tech companies to ask for funds?

PS: I will contribute to the SENS Research Foundation in September of 2015, when I will start milking the Social Security cow. Bear in mind, however, that it takes tens of thousands of poor people like me to give to SENS what one or two billionaires can give. ????

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